Cocaine-use disorders continue to be a significant public health problem in the US. Although there are no FDA-approved pharmacotherapies for cocaine use disorders, some studies of candidate medications have yielded promising results. Given the success in recent years in developing effective pharmacotherapies for alcohol, opioid, and nicotine use disorders, the development of effective pharmacotherapies for cocaine use disorders remains an important public health goal. A recent research trend in substance-use disorder pharmacotherapy is the testing of combinations of agents with different mechanisms to evaluate their potential for synergistic effects. One of the most significant efforts in this line of research is the NIAAA- funded COMBINE Study of naltrexone and acamprosate in the treatment of alcohol dependence. The combination of multiple medications with distinct mechanisms of action has long been accepted into clinical practice in psychiatry and other medical specialties. However, cocaine use disorder pharmacotherapy clinical trials have almost exclusively tested the administration of a single agent. Therefore, we are proposing combining two agents with distinct mechanisms of action that have shown promise in the treatment of cocaine use disorders to determine if the combined therapy is more effective than placebo. The proposed project is a randomized double-blind placebo-controlled trial of extended-release mixed amphetamine salts (ER-MAS) combined with topiramate for the treatment of cocaine dependence. Outpatients meeting DSM-IV criteria for cocaine dependence will enter a one-week placebo lead-in followed by a 12-week prospective, parallel group, randomized, placebo-controlled trial. Following are the specific aims of this study: 1. To determine the efficacy of ER-MAS and topiramate in promoting cocaine abstinence among cocaine- dependent patients. 2. To determine the effect of ER-MAS and topiramate on cocaine craving among cocaine-dependent patients. 3. To explore a set of related secondary outcomes (treatment retention, global functioning, and HIV risk behavior) as well as moderators and mediators potentially reflective of mechanism of action. [unreadable] [unreadable] [unreadable]